Even a few pain pills may be unsafe in heart disease

NEW YORK (Reuters Health) - Some anti-inflammatory painkillers are known to increase heart risks, and new findings from more than 83,000 people suggest that even a couple of days of treatment can be dangerous in people with a history of heart problems.

A group of researchers from Denmark found that people who had experienced a heart attack and took the painkillers, called non-steroidal anti-inflammatory drugs (NSAIDs), had a 45 percent higher risk of having another heart attack or dying within 7 days of treatment.

After 30 days of treatment, the increased risk reached between 55 and 65 percent, relative to people who did not take NSAIDs.

"We demonstrated that short-term treatment with most NSAIDs is associated with increased cardiovascular risk," study author Anne-Marie Schjerning Olsen at Copenhagen University Hospital told Reuters Health. "Our present results indicate that there is no apparent safe therapeutic window for NSAIDs in patients with prior" heart attack.

These findings "fall very much in line" with a 2007 scientific statement from the American Heart Association, co-authored by Dr. Elliott Antman, which also suggested that "none of these (drugs) are safe," Antman told Reuters Health.

When people with heart risks have pain that isn't responding to non-drug interventions, they should "pick the safest drug in the lowest dose needed to control the patient's symptoms, and for the shortest period of time," Antman said.

NSAIDs include over-the-counter medications like aspirin, ibuprofen (marketed as Advil, Motrin and other brands) and naproxen (Aleve), as well as prescription arthritis drugs known as COX-2 inhibitors.

The COX-2 inhibitors were first linked to an increased risk of heart attack and other cardiovascular problems, and two of the drugs -- rofecoxib (Vioxx) and valdecoxib (Bextra) -- were pulled from the market in 2004 and 2005, respectively; a third COX-2 inhibitor, celecoxib (Celebrex) remains on the market.

But subsequent studies also raised concerns about the possible heart risks of some of the older, over-the-counter NSAIDs, including ibuprofen and diclofenac (Voltaren).

To investigate whether even short-term use of NSAIDs carries risks to people who are perhaps more vulnerable, Olsen and her colleagues reviewed national data collected from all Danish residents. They identified more than 83,000 people who had experienced a heart attack, noting who subsequently took NSAIDs, and for how long.

Overall, more than 35,000 participants died or experienced a subsequent heart attack over the course of the study.

More than 40 percent of people took an NSAID after their heart attacks, and even short-term use was associated with more risks, the authors report in the journal Circulation. The most common NSAIDs used were ibuprofen (23 percent) and diclofenac (13 percent).

Not all NSAIDs were associated with the same risks at the same time - ibuprofen, celecoxib, and rofecoxib, for instance, did not come with a higher risk of death or heart attack until after at least 7 to 14 days of treatment. The authors note that people taking the commonly used diclofenac were more at risk early in treatment than those taking rofecoxib, which has been withdrawn from the market over safety concerns.

Naproxen, another over-the-counter NSAID, was not associated with a higher risk of death or heart attack, regardless of the length of treatment.

However, Olsen cautioned in an email that previous research found that people who took naproxen had a higher risk of stomach bleeding than those taking rofecoxib, which can be serious in people with a history of heart attack.

This additional risk of stomach bleeding with NSAID use "further supports a very conservative approach to use of NSAIDs in patients with prior" heart attack, she said.

Unfortunately, Olsen added, the current study does not include information about participants' other risk factors, including blood pressure and body weight, and it's not clear how those might influence the results.

And, importantly, the study does not show that NSAIDs themselves caused any higher risk of heart attack or death, she and her colleagues note - it's possible, for instance, that people who needed to take NSAIDs were generally sicker, and the drug itself is not always behind their higher risks.

In his 2007 statement, Antman and his team ranked painkillers according to which are best for people at risk of cardiovascular problems, starting with the supposedly safest drugs such as acetaminophen and aspirin.

It's good to see other groups looking at this question closely, said the researcher, based at Brigham and Women's Hospital and Harvard Medical School. "We're delighted to see research like this."